Practice in patients undergoing invasive evaluation for coronary artery disease is variable regarding choice of P2Y 12 inhibitor and timing of treatment initiation and is usually dictated by institutional or even individual operator preference. Limited data are available on the actual patterns of P2Y 12 inhibitor use in contemporary practice in the United States. We used electronic medical records from the Cerner “Health Facts” database of adults who underwent coronary angiography with or without percutaneous coronary intervention (PCI) from January 2008 to June 2013 and who received a loading dose of clopidogrel, prasugrel, or ticagrelor at any time from 48 hours before the start of procedure up to 6 hours after. Timing of P2Y 12 inhibitor administration was categorized as >2 hours before, 0 to 2 hours before (pretreatment groups), or after the start of procedure. Results were also evaluated according to type of P2Y 12 inhibitor and patient clinical presentation. A total of 37,964 patients underwent coronary angiography, and 28,306 proceeded to PCI. Pretreatment with a P2Y 12 inhibitor was observed in 28% and 23% in the overall and PCI populations, respectively. Moderate variability of pretreatment rates was noted relative to clinical presentation and P2Y 12 inhibitor type. Pretreatment rates remained fairly constant over time with the exception of a decreasing trend with prasugrel. In conclusion, among patients referred for invasive evaluation of coronary artery disease, P2Y 12 inhibitor pretreatment was low in contemporary US practice, an observation consistent over time and for all available agents and clinical presentations.
All patients undergoing a percutaneous coronary intervention (PCI) require treatment with a platelet P2Y 12 inhibitor. PCI usually follows diagnostic coronary angiography in the same setting (ad hoc PCI), a practice that is followed in over 80% of PCI performed in the United States and is endorsed by the Society of Cardiac Angiography and Interventions. The delayed bioavailability of oral P2Y 12 inhibitors has prompted the practice of initiating treatment before coronary angiography (pretreatment) to ensure that antiplatelet activity would be present should a PCI be required. Randomized trials comparing pretreatment to treatment initiated only after the coronary anatomy is defined, and the decision to proceed with PCI has been made have not conclusively demonstrated a benefit and have even suggested possible harm. In addition, pretreatment may complicate the process of care for the patients who will require coronary bypass grafting surgery (CABG) because they will either have to experience delays to allow for platelet function to return or alternatively proceed to surgery at increased bleeding risk. Guideline recommendations vary, with pretreatment generally considered reasonable in patients with acute coronary syndromes (ACS), except when prasugrel is used. The most recent non–ST-elevation myocardial infarction guidelines released by the European Society of Cardiology reflect the lack of definitive data to support universal pretreatment –“As the optimal timing of ticagrelor or clopidogrel administration in NSTE-ACS patients scheduled for an invasive strategy has not been adequately investigated, no recommendation for or against pretreatment with these agents can be formulated. Based on the Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction (ACCOAST) trial results, pretreatment with prasugrel is not recommended.” We performed this analysis to describe trends of P2Y 12 inhibitor use in contemporary US practice.
Methods
This study used electronic medical records from the Cerner Health Facts database (Cerner, Kansas City, Missouri). Health Facts collects comprehensive, time-stamped clinical and pharmacy records from approximately 300 hospitals and hospital-affiliated outpatient facilities, of diverse size and affiliation (teaching or nonteaching), throughout the US. Patient records in this database have been deidentified in compliance with the Health Insurance Portability and Accountability Act. Adults undergoing diagnostic coronary angiography with or without PCI from January 2008 to June 2013 who received a loading dose of clopidogrel (300 or 600 mg), prasugrel (60 mg), or ticagrelor (180 mg) at any time from 48 hours before the start of procedure up to 6 hours after were included. Procedure time was determined using a proxy of pharmacy dispense times for anesthetics, anxiolytics, contrast media agents, sedatives, or analgesics (in hierarchical order) in a similar manner as has been adopted by the CathPCI registry and published previously. Timing of P2Y 12 inhibitor administration was calculated according to pharmacy dispense time of P2Y 12 inhibitor and procedure time and was further divided into 3 periods: >2 hours before, 0 to 2 hours before, or any time after the start of the procedure. Pretreatment rates (first 2 time categories) were evaluated for the overall study population, but also according to the type of P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and clinical presentation (stable coronary artery disease [SCAD], non–ST-elevation ACS [NSTE-ACS], and ST-elevation ACS [STE-ACS]). This is a descriptive analysis, without a prespecified statistical hypothesis. All analyses were conducted using SAS, version 9.2 (SAS Institute Inc., Cary, North Carolina).
Results
A total of 37,964 patients from 77 hospitals (18, 27, 25, and 7 hospitals from the 4 census regions of the Midwest, Northeast, South, and West, respectively) met the entry criteria and were included in the analysis. The patient breakdown according to clinical presentation was 22,631 (59.6%) with SCAD, 8,885 (23.4%) with NSTE-ACS, and 6,448 (17.0%) with STE-ACS. A total of 28,306 patients (74.6%) underwent angiography and PCI, whereas 9,658 patients (25.4%) underwent only diagnostic coronary angiography.
Overall, 27.8% of patients included in this analysis received pretreatment (14.6% >2 hours, 13.2% within 0 to 2 hours). Although there was moderate variability relative to P2Y 12 inhibitor type, overall, pretreatment was more frequent in STE-ACS and NSTE-ACS than in SCAD ( Figure 1 , Top ). Pretreatment rates were also low at 23.1% in the subgroup of the 28,306 patients that proceeded to PCI with similar patterns of distribution according to P2Y 12 inhibitor type or clinical presentation as observed in the overall study population ( Figure 1 , Bottom).
Practice patterns remained fairly consistent over time without important difference in pretreatment rates from 2008 to 2013. This stable pattern of pretreatment over time was true for all clinical presentations ( Figure 2 , Left ). There seemed to be a trend toward lower rates of pretreatment over time with the newer agents, especially prasugrel, but in the case of clopidogrel pretreatment rates remained stable over time ( Figure 2 , Right).
Finally, our analysis showed that clopidogrel had been and still was the most commonly used P2Y 12 inhibitor in this population and even as recently as 2013 was still used in over 3/4 of patients in this database. The use of prasugrel appeared to have stabilized at about 13%, whereas the adoption of ticagrelor appeared to be slowly increasing over time and was at about 10% by 2013 ( Figure 3 , Top Left). Consistent with product labels and practice guidelines, the use of prasugrel and ticagrelor was higher in patients with STE-ACS and NSTE-ACS (15.6% and 11.8%, respectively) compared with patients with SCAD (11.6% and 7.3%, respectively; Figures 3 , Top Right and Bottom).
